| RRC ID |
84082
|
| Author |
Zhao C, Cai S, Shi R, Li X, Deng B, Li R, Yang S, Huang J, Liang Y, Lu P, Yuan Z, Jia H, Jiang Z, Zhang X, Kennedy S, Wan G.
|
| Title |
HERD-1 mediates multiphase condensate immiscibility to regulate small RNA-driven transgenerational epigenetic inheritance.
|
| Journal |
Nat Cell Biol
|
| Abstract |
Biomolecular condensates, such as the nucleolus, stress granules/processing bodies and germ granules, are multiphase assemblages whose formation mechanisms and significance remain poorly understood. Here we identify protein constituents of the spatiotemporally ordered P, Z and M multiphase condensates in Caenorhabditis elegans germ granules using optimized TurboID-mediated proximity biotin labelling. These include 462, 41 and 86 proteins localizing to P, Z and M condensates, respectively, of which 522 were previously unknown protein constituents. Each condensate's proteins are enriched for distinct classes of structured and intrinsically disordered domains, suggesting divergent functions and assembly mechanisms. Through a functional screen, we identify a germ granule protein, HERD-1, which prevents the mixing of P, Z and M condensates. Mixing in herd-1 mutants correlates with disorganization of germline small RNA pathways and prolonged epigenetic inheritance of RNA interference-induced gene silencing. Forced mixing of these condensate components using a nanobody with specific binding activity against green fluorescent protein also extends epigenetic inheritance. We propose that active maintenance of germ granule immiscibility helps to organize and regulate small RNA-driven transgenerational epigenetic inheritance in C. elegans.
|
| Volume |
26(11)
|
| Pages |
1958-1970
|
| Published |
2024-11-1
|
| DOI |
10.1038/s41556-024-01514-8
|
| PII |
10.1038/s41556-024-01514-8
|
| PMID |
39354132
|
| MeSH |
Animals
Biomolecular Condensates / genetics
Biomolecular Condensates / metabolism
Caenorhabditis elegans* / genetics
Caenorhabditis elegans* / metabolism
Caenorhabditis elegans Proteins* / genetics
Caenorhabditis elegans Proteins* / metabolism
Cytoplasmic Granules / genetics
Cytoplasmic Granules / metabolism
Epigenesis, Genetic*
Germ Cells* / metabolism
Inheritance Patterns
Mutation
RNA Interference
|
| Resource |
| C.elegans |
tm1200 |
